Perinatal nicotine exposure alters AT 1 and AT 2 receptor expression pattern in the brain of fetal and offspring rats.
The present study determined the effect of maternal nicotine exposure during the early developmental period on AT(1)R and AT(2)R mRNA and protein abundance in the rat brain. Pregnant rats of day-4 gestation were implanted with osmotic minipumps that delivered nicotine at a dose rate of 6 mg/kg/day for 28 days. Neither fetal nor offspring brain weight was significantly altered by the nicotine treatment. Nicotine significantly increased brain AT(1)R in fetuses at gestation 15 and 21 days and decreased central AT(2)R at gestation day 21. In the offspring, perinatal nicotine significantly increased brain AT(1)R protein in males but not females at 30 days, and increased it in both males and females at 5-month-old. AT(2)R protein levels were significantly decreased by nicotine in both male and female offspring regardless of ages. Whereas brain AT(1)R mRNA abundance did not change during postnatal development, AT(2)R mRNA levels in both sexes significantly decreased in 5-month-old, as compared with 30-day-old offspring. Nicotine significantly increased brain AT(1)R mRNA in the female offspring. In contrast, it decreased AT(2)R mRNA in the brain to the same extent in males and females. In control offspring, there was a developmental increase in the AT(1)R/AT(2)R mRNA ratio in the brain of adult animals, which was significantly up-regulated in nicotine-treated animals with females being more prominent than males. The results demonstrate that perinatal nicotine exposure alters AT(1)R and AT(2)R gene expression pattern in the developing brain and suggest maternal smoking-mediated pathophysiological consequences related to brain RAS development in postnatal life.
Mao
Caiping
C
Perinatal Biology Center, Soochow University School of Medicine, Suzhou, PR China.
Zhang
Hong
H
Xiao
Daliao
D
Zhu
Liyan
L
Ding
Yang
Y
Zhang
Yuying
Y
Wu
Lei
L
Xu
Zhice
Z
Zhang
Lubo
L
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D012907:Smoking / Q000009:adverse effects; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D018722:Nicotinic Agonists; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D009538:Nicotine